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Abstract: Background: Neoplastic seeding of hepatocellular carcinoma may arise after radiofrequency ablation. Aims: In order to clarify the real risk of seeding, we observed a prospective cohort of patients undergoing radiofrequency ablation. Methods: Ninety-three (22.9%) out of 406 consecutive patients with hepatocellular carcinoma superimposed to cirrhosis diagnosed at our Liver Unit (2000–2005) were selected for radiofrequency ablation according to the Barcelona 2000 EASL guidelines. Seventy-one patients were treated by a percutaneous approach and 22 at laparotomy. After radiofrequency ablation ultrasound scan was repeated every 3 months and spiral-computed tomography every 6 months. Results: Overall 145 sessions were performed in 93 patients: 113 (77.9%) by a percutaneous approach and 32 (22.1%) at laparotomy. The median follow-up was 23 months (range 1–60). Only 1 of the 71 patients (1.4%; 95% C.I. 0.25–7.56) treated percutaneously and none of the 22 (0%; 95% C.I. 0–14.8) treated at laparotomy showed neoplastic seeding. Conclusion: In our experience the risk of seeding of hepatocellular carcinoma after radiofrequency ablation was small (1.1% per patient, 95% C.I. 0.19–5.84; 0.7% per procedure, 95% C.I. 0.12–3.80). A stringent selection of patients for radiofrequency ablation and retraction of the needle with a hot tip may have been instrumental in obtaining this low frequency. [Copyright &y& Elsevier]